NM_001034832.5:c.98C>A

Variant names:

• chrX-48410836-G-T
• rs371037826
• NM_001034832.5:c.98C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001034832.5(SSX4B):​c.98C>A​(p.Ser33Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.00012 (0 hom. 0 hem.)
• Consequence: SSX4B NM_001034832.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.05
• Publications: 0 publications found

Genes affected

SSX4B (HGNC:16880): (SSX family member 4B) The product of this gene belongs to the family of highly homologous synovial sarcoma X (SSX) breakpoint proteins. These proteins may function as transcriptional repressors. They are also capable of eliciting spontaneously humoral and cellular immune responses in cancer patients, and are potentially useful targets in cancer vaccine-based immunotherapy. SSX1, SSX2 and SSX4 genes have been involved in the t(X;18) translocation characteristically found in all synovial sarcomas. This translocation results in the fusion of the synovial sarcoma translocation gene on chromosome 18 to one of the SSX genes on chromosome X. Chromosome Xp11 contains a segmental duplication resulting in two identical copies of synovial sarcoma, X breakpoint 4, SSX4 and SSX4B, in tail-to-tail orientation. This gene, SSX4B, represents the more centromeric copy. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17372376).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034832.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSX4B	NM_001034832.5	MANE Select	c.98C>A	p.Ser33Tyr	missense	Exon 3 of 8	NP_001030004.1
	SSX4B	NM_001040612.4		c.98C>A	p.Ser33Tyr	missense	Exon 3 of 7	NP_001035702.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSX4B	ENST00000595235.6	TSL:1 MANE Select	c.98C>A	p.Ser33Tyr	missense	Exon 3 of 8	ENSP00000469394.1	O60224-1
	SSX4B	ENST00000619890.1	TSL:5	c.98C>A	p.Ser33Tyr	missense	Exon 3 of 7	ENSP00000481765.1	O60224-2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.0000455 AC: 8 AN: 175920 AF XY: 0.00

Gnomad AFR exome AF: 0.0000816

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000124 AC: 82 AN: 661991 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 160257

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000587 AC: 1 AN: 17029

American (AMR) AF: 0.00 AC: 0 AN: 13847

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9254

East Asian (EAS) AF: 0.00 AC: 0 AN: 15517

South Asian (SAS) AF: 0.00 AC: 0 AN: 32285

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1508

European-Non Finnish (NFE) AF: 0.000149 AC: 78 AN: 522284

Other (OTH) AF: 0.000113 AC: 3 AN: 26521

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ESP6500AA AF: 0.000263 AC: 1

ESP6500EA AF: 0.000299 AC: 2

ExAC AF: 0.0000577 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	21
DANN	Uncertain	0.99
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.0
PrimateAI	Uncertain	0.69	T
Sift4G	Pathogenic	0.0010	D
Vest4		0.58
MVP		0.030
ClinPred		0.12	T
GERP RS		0.71
gMVP		0.18
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs371037826; hg19: chrX-48270279;